It has been proposed that environmental factors may alter immune function indirectly by affecting other organ systems that impact on immune function. Results have shown that norepinephrine, via beta-2-adrenoceptor stimulation, increases the number of antigen-specific B lymphocyte precursors differentiating into antibody-secreting cells, without affecting the number of antibody-secreting cells produced by each precursor. In addition, as part of a collaborative project with LMIN, results have shown that T and B lymphocyte function is altered after exposure to neuropeptide fragments derived from proenkephalin, and that both T and B lymphocytes produce and secrete the precursor peptide. Thus, a xenobiotic-induced alteration of one organ system may precipitate dysfunction in another by affecting the secretion of multi-targeted modulatory molecules. To address these questions in vivo, an animal model has been established that utilizes the scid mouse reconstituted with the same lymphocytes used in vitro. Preliminary results have shown that these mice secrete antibody after primary immunization and survive neurotransmitter depletion with 6- hydroxydopamine. These studies have implications for basic biomedical and clinical research on brain-immune interactions. An understanding of integrated system function will contribute to an increased understanding of immune and neuroendocrine function, and will contribute to the development of targeted drug strategies to prevent toxicities that may result from exposure of an integrated biological system to environmental factors.